This project aims to understand the functions and actions of descending neural systems to the cochlea and cochlear nucleus. A particular focus is the olivocochlear (OC) neurons, which are divided into medial (MOC) and lateral (LOC) subgroups. These neurons project from the superior olivary complex to the cochlea, with MOC endings formed on outer hair cells and LOC endings formed mainly on the dendrites of auditory-nerve fibers beneath inner hair cells. We will study, in Aim 1A, MOC actions on outer hair cells using otoacoustic emission tests, to gain insight into parallel results in humans. The results will allow us to infer the physiological and anatomical characteristics of human MOC neurons. Using recordings and labeling of MOC single units, we will study, in Aim 1B, the characteristics of MOC Contra units, which respond to sound in the ear contralateral to the one that receives their axonal projections. These results will give us insight as to how the MOC contralateral reflex differs from that to ipsilateral sound. We will study, in Aim 1C, the MOC innervation of the human cochlea. This aim has particular relevance for interpretation of human otoacoustic emission tests, and it is made possible by recent advances that allow us to remove the embedding medium, celloidin, from human sections and then immunostain them. We will, in Aim 2A, use new techniques and an assay that allows us to observe small, potentially LOC-induced changes on auditory-nerve response following reversible hearing loss where we can measure responses on the previously plugged ipsilateral side. We will, in Aim 2B, use a new mouse strain, ChAT-cre driving tdTomato to visualize neural inputs to LOC dendrites. These data will allow us to specify the inputs to LOC neurons, much as we have done for MOC neurons and motoneurons of the middle ear muscles in the previous grant period. With this knowledge, we will better know the neural mechanisms of the olivocochlear neurons and how they function to provide protection, reduce masking, and provide other functions relevant to the workplace and to everyday life.